Pityriasis lichenoides chronica induced by infliximab, with response to methotrexate

ARTICLE

Auteur(s) : Anna López-Ferrer¹, Luis Puig¹, Gerardo Moreno², Alejandro Camps-Fresneda², José Palou³, Agustín Alomar¹

¹Department of Dermatology, Hospital de la Santa Creu i Sant Pau, Sant Antoni Maria Claret 167, 08025 Barcelona, Spain
²Dermalas, Clínica Teknon, Barcelona, Spain
³Unitat de Dermatopatologia, Barcelona, Spain

Infliximab, a chimeric monoclonal antibody that binds to free and membrane-bound tumor necrosis factor (TNF)-α, has been demonstrated to be effective in treating immune-mediated inflammatory diseases, such as psoriasis, rheumatoid arthritis and inflammatory bowel disease. Infusion reactions are the most frequent adverse effect, but paradoxical psoriasiform and pustular rashes can be observed rather frequently. Keratosis folicularis, leukocytoclastic vasculitis, dermatitis herpetiformis, alopecia, folliculitis, perniosis-like eruptions, granuloma annulare and sarcoidosis have also been reported [1]. Until now, there is only one report describing the appearance of pityriasis lichenoides chronica (PLC) in association with infliximab treatment in a patient with severe psoriasis [2].

Here we report the case of a 53-year-old man with spondyloarthritis associated to ulcerative colitis of 3 years’ evolution, which had been unresponsive to salazopyrine. He started treatment with infliximab 5 mg/kg at weeks 0, 2, 6 and every 8 weeks, with marked clinical improvement by 4 weeks. Several days after the fourth infusion, approximately 50 erythemato-desquamative papules, 4 to 9 mm in diameter, appeared on the trunk, arms, buttocks and proximal areas of the legs (figure 1A). The patient was asymptomatic and afebrile. He had no personal or family history of psoriasis or other skin diseases, and he had not received any other concomitant medication. Bacterial cultures from skin scrapings were negative, cell blood counts and serum biochemical parameters were normal, and a rapid plasma reagin test was negative. Histopathological examination of a skin biopsy specimen showed epidermal hyperkeratosis with parakeratosis, acanthosis and spongiosis, with vacuolar changes in the basal layer and a perivascular lymphocytic infiltrate. Extravasated red blood cells were seen in both the upper dermis and the epidermis. These findings were consistent with the diagnosis of pityriasis lichenoides (figure 1B).

Treatment with oral methotrexate 15 mg per week was initiated. After one month of treatment, the rash had disappeared and methotrexate was stopped. Infliximab 5 mg/kg every 8 weeks was continued, with maintenance of clinical response. Neither skin lesions nor any other adverse events have appeared after 6 months of follow-up.

Several skin reactions have been reported in association with anti- TNF-α treatments for various indications [1]. Recently, Newell et al. [2] reported the appearance of PLC in a patient with psoriasis after the third infusion of infliximab; 5 months after the first infusion, psoriasis became blanched but the PLC remained active. Ben Said et al. [3] have reported two cases of PLC in patients with Crohn's disease under treatment with adalimumab [3]. In both cases complete remission was achieved in 2-3 weeks following the introduction of methotrexate therapy (7.5 mg/week), and adalimumab treatment could be maintained. In one of these cases, PLC recurred following methotrexate discontinuation, and remission was achieved following reintroduction of methotrexate. In our case, following the appearance of PLC, methotrexate 15 mg/week was started, with excellent results after one month of treatment. Even though a spontaneous resolution cannot be ruled out, our experience is consistent with that of Ben Said et al. [3].

To date, the etiology of pityriasis lichenoides and its variants is unknown, but TNF-α appears to be involved in its pathogenesis, as suggested by the increased serum levels found in a patient with febrile ulceronecrotic Mucha-Habermann disease [4] and the therapeutic effect of etanercept in one case of treatment-refractory pityriasis lichenoides [5].

In our view, the appearance of PLC in the course of treatment with TNF-α blocking agents might be considered a paradoxical phenomenon, like psoriasiform eruptions and palmoplantar pustulosis which have been reported to occur as both class-specific and drug-specific cutaneous adverse events of TNF-α blocking agents [6]. If this is the case, methotrexate represents an interesting therapeutic option, allowing continuation of anti-TNF-α treatment; but the risks and benefits of this combination in patients with rheumatological disease, inflammatory bowel disease and psoriasis must be carefully weighed.

Acknowledgements

References

2 Newell EL, Jain S, Stephens C, Martland G. Infliximab-induced pityriasis lichenoides chronica in a patient with psoriasis. JEADV 2009; 23: 169-243.

3 Said BB, Kanitakis J, Graber I, Nicolas JF, Saurin JC, Berard F. Pityriasis lichenoides chronica induced by adalimumab therapy for Crohn's disease: Report of 2 cases successfully treated with methotrexate. Inflamm Bowel Dis. 2009 Oct 9. [Epub ahead of print]

4 Tsianakas A, Hoeger PH. Transition of pityriasis lichenoides et varioliformis acuta to febrile ulceronecrotic Mucha-Habermann disease is associated with elevated serum tumour necrosis factor-alpha. Br J Dermatol 2005; 152: 794-9.

5 Nikkels AF, Gillard P, Piérard GE. Etanercept in therapy multiresistant overlapping pityriasis lichenoides. J Drugs Dermatol 2008; 7: 990-2.

6 Bremmer M, Deng A, Gaspari AA. A mechanism-based classification of dermatologic reactions to biologic agents used in the treatment of cutaneous disease: Part 2. Dermatitis 2009; 20: 243-56.